Objective To observe the expression of uPA, tPA and PAI-1 in whole blood of rat membranous nephropathy (MN) models induced by cationic bovine serum albumin (C-BSA), and to explore the effect of fibrinolytic system on podocyte apoptosis and pathological changes. To explore the possible preventive and therapeutic effects and the possible mechanisms of early prevention of fibrinolysis. Methods We developed a MN model with the modified Border method. At the end of the 1st, 2nd, 3th, and 4th week of immunization, respectively, the levels of whole blood uPA, tPA and PAI-1 were determined by ELISA. The rat kidney tissues were examined by light microscopy and electron microscopy to identify the pathological changes. The expression levels of nephrin and WTl were detected with immumofluorescence staining and their correlation was analyzed. Results Compared the treatment group with control group, the levels of whole blood uPA, tPA and PAI-1 of the model group were decreased, while PAI-1 was elevated, showing a significant difference (P < 0.05). The degree of renal interstitial fibrosis was more serious. Correlation analysis showed that the whole blood tPA and uPA levels were positively correlated with the changes of nephrin protein expression in the kidney tissue, while the whole blood PAI-1 level was negatively correlated with the nephrin protein expression in the kidney tissue. Conclusions In the process of MN development, the fibrinolytic system may have important significance for podocyte apoptosis. Determination of early phase of MN podocyte injury may be another therapy target for prevention of the disease development, and then provide new ideas for clinical research and drug development for MN.